Nitidine chloride, a benzophenanthridine alkaloid from Zanthoxylum nitidum (Roxb.) DC., exerts multiple beneficial properties, especially in tumors and inflammation-related diseases

Abstract

Plant-derived alkaloids are a kind of very important natural organic compounds. Nitidine chloride is one of the main active ingredients in Zanthoxylum nitidum (Roxb.) DC. which is a frequently-used Chinese herbal medicine. Z. nitidum has many kinds of efficacy, such as activating blood circulation and removing stasis, promoting qi circulation and relieving pain, and detoxication and detumescence. In China, Z. nitidum is usually used for the treatment of gastrointestinal diseases, toothache, and traumatic injury. At present, there are numerous studies of nitidine chloride with regard to its pharmacology, pharmacokinetics, toxicology, etc. However, a systematic, cutting-edge review of nitidine-related studies is extremely lacking. The present paper aimed at comprehensively summarizing the information on the extraction, separation and purification, pharmacology, pharmacokinetics, toxicology and formulation of nitidine chloride. The knowledge included in the present study were searched from the following academic databases involving Web of Science, PubMed, Google scholar, Elsevier, CNKI and Wanfang Data, till July 2022. In terms of nitidine chloride extraction, enzymatic method and ultrasonic method are recommended. Resin adsorption and chromatography were usually used for the separation and purification of nitidine chloride. Nitidine chloride possesses diversified therapeutical effects, such as anti-tumor, anti-inflammation, anti-colitis, anti-malaria, anti-osteoporosis, anti-rheumatoid and so on. According to pharmacokinetics, the intestinal absorption of nitidine chloride is passive diffusion, and it is rarely excreted with urine and feces in the form of prototype drug. Nitidine chloride has a moderate binding to plasma protein, which is independent of the drug concentration. As to toxicology, nitidine chloride showed certain toxicity on liver, kidney and heart. Certain new formulations, such as nanoparticle, microsphere and nano-micelle, could increase the therapeutic effect and decrease the toxicity of nitidine chloride. Despite limitations such as poor solubility, low bioavailability and certain toxicity, nitidine chloride is still a promising natural alkaloid for drug candidates. Extensive and intensive exploration on nitidine chloride is essential to promote the usage of nitidine-based drugs in the clinic practice.

Green Alternatives in Treatment of Liver Diseases: the Challenges of Traditional Medicine and Green Nanomedicine

“…[41,42] Other phytocompounds used for the treatment of liver cancer, for example, the alkaloid Nitide Chloride, also have low water solubility, low bioavailability, and mild toxicity. [43] It was shown that the increased consumption of alcohol in the preparation called "herbal wine" combined with resveratrol might be a cause of increased liver damage and necrosis since alcohol decreases the absorption of resveratrol by 95 %, which decreases its therapeutic effects. It also increases alcohol absorption by 126 % and inhibition of the ethanol metabolic pathway.…”

“… [39] Echinacoside, a metabolite obtained from Cistanche tubulosa , has activity against hepatocellular cancer, [40] but despite these properties, when administered orally, it has poor absorption and low bioavailability [41,42] . Other phytocompounds used for the treatment of liver cancer, for example, the alkaloid Nitide Chloride, also have low water solubility, low bioavailability, and mild toxicity [43] …”

Discovery of Topoisomerase I Inhibitor Nitidine Derivatives with IL-10 Enhancing Activity for the Treatment of Sepsis

“…DC root, has anticancer, anti-inflammatory, antimalarial, and antibacterial properties. [11][12][13][14][15][16][17] In our previous study, we selected more than 500 monomeric compounds related to the development, differentiation, and functions of macrophages from the Chinese medicine compound library based on a screening platform. 11 We found that at a noncytotoxic dose (0-4 μmol/L), NC potentially prevented sepsis, and the underlying mechanisms may be the inhibition of TopoI, the induction of repairable DNA damage, and the subsequent activation of DNA damage response and the promotion of Akt activation.…”

“…11 However, the application of NC is limited due to its poor water solubility and low bioavailability. 12,18 Water solubility is an essential physicochemical property of an organic smallmolecule drug. It is also an important issue during the drug discovery.…”

Nitidine Chloride Triggers Autophagy and Apoptosis of Ovarian Cancer Cells through Akt/mTOR Signaling Pathway

“…In the field of anti-tumor, it is found that NC can affect and regulate the growth of breast cancer, lung cancer, liver cancer, gastric cancer, etc . [ 19 ], but research in ovarian cancer is still relatively scarce. The existing literature mainly focuses on NC's influence on the proliferation of ovarian cancer cells through ERK, AKT, and Fas pathways [ 20 , 21 ], but few researchers have found out whether NC affects autophagic apoptosis of ovarian cancer cells through regulating signal pathways.…”